This invention relates to lipid emulsion compositions and to methods of treating systemic toxicity by reducing the bioavailability of pharmaceuticals, poisons and other foreign agents present in the circulation by the intravenous infusion of a lipid emulsion composition. Of particular interest are methods and compositions to treat patients having adverse reactions to pharmaceutical drugs such as anesthetics or antidepressants. Anesthetics and similar substances can have severe adverse effects, particularly cardiovascular effects, if present in improper amounts. In cases of overdoses or allergic reactions, such effects can include heart failure and even death.
An emulsion is a collective of lipid or oil microparticles dispersed in water usually by the action of an emulsifying agent. Historically, emulsions have been widely used in the cosmetic and drug industries in connection with creams, depilatories, antiperspirants, deodorants, antiseptics and the like. Emulsion systems which include sugars, amino acids, vitamins, and electrolytes have also been utilized as a means of providing intravenous nutrition in order to maintain a patient's life when oral or nasal feeding is impossible or insufficient (see U.S. Pat. No. 5,674,527 to Inoue et al.). Another common use of emulsions is in parenteral drug delivery systems (see U.S. Pat. No. 3,538,216 to Polin et al.). These drug delivery systems feature hydrophobic medicinals suspended in an emulsion to be delivered to the patient in a sustained release manner. The lipid emulsion in this system consists of a thixotropic agent, a gelatinous-oil composition containing an ion-exchange agent, and water.
Also, edible but non-digestible emulsions have been used as traps for toxins present in the gastrointestinal (GI) tract as described in U.S. Pat. No. 4,183,918 to Asher et al. In this trap system, the emulsion is fed to a symptomatic patient wherein the toxins are removed by the action of the absorbent-containing emulsion passing through the GI tract. Key features of this system include the use of non-digestible oils as the exterior phase of the emulsion and the use of a reactant or adsorbent in the interior aqueous phase of the emulsion. Examples of exterior phase oils used in this system include highly refined hydrocarbon oils, mineral oils, and silicone oils, while preferred interior phase reactants and adsorbents include silica gel and carbon.
Other means of detoxifying the body include the delivery of liposomes containing active reagents to a patient. For example, an aqueous solution of the chelating agent EDTA was encapsulated by liposomes (synthetic membrane vesicles) and given to a patient undergoing chemotherapy in order to remove the radioactive metal plutonium from the patient's body. (Rahman et al., Science (1973) 180:300). Liposomes, in most cases, act by rupturing their membranes to release their inner contents. As such, liposomes have also been used to deliver drugs in a controlled release manner as described in U.S. Pat. No. 4,837,028 to Allen. However, liposomes are not readily permeable to extraneous toxic agents present in the body.
In light of the foregoing, a need remains for materials and methods to effectively decrease the bioavailability of foreign toxic substances in the bloodstream, especially lipophilic or amphiphilic agents such as antidepressants, anesthetics, alcohol, cocaine or others which require immediate intervention when present in dangerous amounts.